Cerebrotendinous xanthomatosis, sitosterolemia, Smith-Lemli-Opitz syndrome and the seminal contributions of Gerald Salen, MD (1935-2020).

Cerebrotendinous xanthomatosis (CTX), sitosterolemia, and Smith-Lemli Opitz syndrome (SLOS) are rare inborn errors of metabolism. The diagnoses of CTX and sitosterolemia are often delayed for many years because of lack of physician awareness, often resulting in significant and unnecessary progression of disease. CTX may present with chronic diarrhea, juvenile onset cataracts, strikingly large xanthomas, and neurologic disease in the setting of a normal serum cholesterol, but markedly elevated serum or plasma cholestanol levels. These patients have a defect in producing the bile acid chenodoxycholate, and oral chenodeoxycholate therapy is essential for these patients in order to prevent neurologic complications. Sitosterolemia can present with xanthomas, anemia, thrombocytopenia, splenomegaly, very premature heart disease, and serum cholesterol levels that may be normal or elevated, along with marked elevations of plasma ß-sitosterol. These patients have a defect causing overabsorption of ß-sitosterol, and the treatment of choice is oral ezetimibe. SLOS presents with growth delay, intellectual disability, multiple structural anomalies, and low serum cholesterol levels, and the defect is reduced cholesterol production. Treatment consists of dietary cholesterol supplementation and oral bile acid therapy which raises serum cholesterol levels and may improve symptoms. The metabolic and genetic defects in these disorders have been defined. There is no one in our field that has contributed more to the diagnosis and treatment of these disorders than Gerald Salen, MD, who died in late 2020 at 85 years of age. He will be greatly missed by his family, friends, and colleagues from around the world.

Sitosterolemia: Twenty Years of Discovery of the Function of ABCG5ABCG8.

Sitosterolemia is a lipid disorder characterized by the accumulation of dietary xenosterols in plasma and tissues caused by mutations in either ABCG5 or ABCG8. ABCG5 ABCG8 encodes a pair of ABC half transporters that form a heterodimer (G5G8), which then traffics to the surface of hepatocytes and enterocytes and promotes the secretion of cholesterol and xenosterols into the bile and the intestinal lumen. We review the literature from the initial description of the disease, the discovery of its genetic basis, current therapy, and what has been learned from animal, cellular, and molecular investigations of the transporter in the twenty years since its discovery. The genomic era has revealed that there are far more carriers of loss of function mutations and likely pathogenic variants of ABCG5 ABCG8 than previously thought. The impact of these variants on G5G8 structure and activity are largely unknown. We propose a classification system for ABCG5 ABCG8 mutants based on previously published systems for diseases caused by defects in ABC transporters. This system establishes a framework for the comprehensive analysis of disease-associated variants and their impact on G5G8 structure-function.

Quinolone nonsusceptibility among enteric pathogens isolated from international travelers - Foodborne Diseases Active Surveillance Network (FoodNet) and National Antimicrobial Monitoring System (NARMS), 10 United States sites, 2004 - 2014.

Gastrointestinal illnesses are the most frequently diagnosed conditions among returning U.S. travelers. Although most episodes of travelers' diarrhea do not require antibiotic therapy, fluoroquinolones (a type of quinolone antibiotic) are recommended for treatment of moderate and severe travelers' diarrhea as well as many other types of severe infection. To assess associations between quinolone susceptibility and international travel, we linked data about isolate susceptibility in NARMS to cases of enteric infections reported to FoodNet. We categorized isolates as quinolone-nonsusceptible (QNS) if they were resistant or had intermediate susceptibility to ≥1 quinolone. Among 1,726 travel-associated infections reported to FoodNet with antimicrobial susceptibility data in NARMS during 2004-2014, 56% of isolates were quinolone-nonsusceptible, of which most (904/960) were Campylobacter. International travel was associated with >10-fold increased odds of infection with quinolone-nonsusceptible bacteria. Most QNS infections were associated with travel to Latin America and the Caribbean (390/743; 52%); however, the greatest risk of QNS infection was associated with travel to Africa (120 per 1,000,000 passenger journeys). Preventing acquisition and onward transmission of antimicrobial-resistant enteric infections among travelers is critical.

Early History of Home Parenteral Nutrition: From Hospital to Home.

Technologic advances in the past century have led to the ability to safely deliver parenteral nutrition (PN) to hospitalized patients. Key breakthroughs included the development of saline and glucose infusions, infusion pumps, macronutrients (lipids, dextrose, and amino acids), and central venous catheters. In the 1960s, centrally delivered PN was performed in short-term hospitalized patients by Lincoln James Lawson (North Staffordshire Royal Infirmatory, United Kingdom) and long-term patients by Stanley Dudrick (University of Pennsylvania, United States). These early studies showed that a system was needed that would allow patients with intestinal failure to be discharged from the hospital and receive home PN (HPN). In the late 1960s and early 1970s, Belding Scribner, Maurice Shils, Khursheed Jeejeebhoy, Marvin Ament, Dudrick, and their teams discharged patients from the hospital who then self-administered HPN. Shortly after these early cases of HPN, multidisciplinary centers were established first in North America, and later in Europe, to manage these complex cases. The current article describes the patients treated by these early HPN pioneers, in addition to subsequent case series reported by them and others.

Denis Burkitt and the origins of the dietary fibre hypothesis.

For more than 200 years the fibre in plant foods has been known by animal nutritionists to have significant effects on digestion. Its role in human nutrition began to be investigated towards the end of the 19th century. However, between 1966 and 1972, Denis Burkitt, a surgeon who had recently returned from Africa, brought together ideas from a range of disciplines together with observations from his own experience to propose a radical view of the role of fibre in human health. Burkitt came late to the fibre story but built on the work of three physicians (Peter Cleave, G. D. Campbell and Hugh Trowell), a surgeon (Neil Painter) and a biochemist (Alec Walker) to propose that diets low in fibre increase the risk of CHD, obesity, diabetes, dental caries, various vascular disorders and large bowel conditions such as cancer, appendicitis and diverticulosis. Simply grouping these diseases together as having a common cause was groundbreaking. Proposing fibre as the key stimulated much research but also controversy. Credit for the dietary fibre hypothesis is given largely to Burkitt who became known as the 'Fibre Man'. This paper sets out the story of the development of the fibre hypothesis, and the contribution to it of these individuals.

[The role of sanitary conditions in the Apulian aquedoct construction policy in Bari]. / Il ruolo delle condizioni igienicosanitarie a Bari nella politica di costruzione dell'acquedotto pugliese.

In the city of Bari (Italy), during the 19th century, energetic political battles were carried out between the administrators and governors in order to ensure the population the primary resource for life: the water. In this town, there were no rivers or drinking water sources; the thirsty population drank from public and private cisterns for collecting rainwater. The condition of the pavement, poor maintenance of the reservoirs and the presence of absorbent cesspits in the vicinity of the wells were often the cause of pathogenic microorganisms' infiltration, such as viruses, bacteria or parasites, which were responsible for the most common digestive disorders. This paper aims to highlight the ties between political campaigns for the construction of the aqueduct and the recognition by the scientific community and governors of the causal link between certain diseases and infected water. The case of the city of Bari is exemplary because, according to the statistics of the causes of death, the hygienic conditions of the city changed parallel to the development of urban infrastructures, which radically intensified with the construction of the Apulian aqueduct in 1915, and the sewage system in 1920.

Isaac Albeniz (1860-1909): Spanish musician who died of chronic renal disease.

Isaac Albéniz was a Spanish musician and pianist who was best known in France and England. One of his last works for piano, the suite Iberia, is well-known and identifies his country of origin. He died with terminal uraemia following longstanding chronic intestinal and kidney symptoms. Suggestions as to pathology include amyloidosis complicated by kidney stones and hypertension that sometimes manifested itself in the form of hypertensive crisis, accompanied by obesity.

Study on traditional Chinese medicine theory of lung being connected with large intestine.

OBJECTIVE: The theory of lung being connected with large intestine, which is a major topic in Traditional Chinese Medicine (TCM), has guided clinical practice for thousands of years in China. METHODS: In this study, we analyzed the history, main contents, clinical application, and material basis of the theory, to attempt to improve the potential clinical significance of "lung being connected with large intestine" in China. RESULTS: The lung being connected with large intestine was first described in "Huang Di Nei Jing", and formed one of the basic theories of TCM. For thousands of years, the majority of TCM practitioners explored this theory continuously, leading to its development and use as an important theory in the guidance of TCM clinics In the last decade, researchers in the field of integrated TCM and Western medicine have studied clinical applications and biomedical mechanisms with experimental methods to explore the implications of the theory. CONCLUSION: With the further development of science and technology, research concerning the theory of lung being connected with large intestine will be greatly stimulated and contribute to the modernization of TCM.

Intestinal failure: A new era in clinical management.

Only 50 years ago intestinal failure was considered incompatible with life. Since then, developments in parenteral nutrition, and, more recently, small intestinal transplantation, have provided new therapeutic options with the potential to offer long-term survival with a good quality of life. Current medical and surgical strategies are aimed at enhancing intestinal adaptation, improving absorption to achieve nutritional independence, and minimizing the complications of parenteral nutrition therapy. An integrated, multidisciplinary approach to the management of patients with intestinal failure, closely linked to a transplantation program to facilitate early referral, is recognized as a key factor in optimizing patient outcomes.

Transforming public health?: a critical review of progress made against enteric diseases during the American-led occupation of Japan (1945-52).

Historical assessments of the Occupation's efforts to tackle enteric diseases (cholera, typhoid, paratyphoid and dysentery) have generally reflected a celebratory narrative of US-inspired public health reforms, strongly associated with the head of the Public Health and Welfare Section, Crawford F. Sams. Close inspection of the documentary record, however, reveals much greater continuity with pre-war Japanese public health practices than has hitherto been acknowledged. Indeed, there are strong grounds for disputing American claims of novelty and innovation in such areas as immunisation, particularly in relation to typhoid vaccine, and environmental sanitation, where disparaging comments about the careless use of night soil and a reluctance to control flies and other disease vectors reveal more about the politics of public health reform than the reality of pre-war practices. Likewise, the representation of American-inspired sanitary teams as clearly distinct from and far superior to traditional sanitary associations (eisei kumiai) was closer to propaganda than an accurate rendering of past and present developments.

Colorectal carcinoma that afflicted King Jehoram.

This research uses the tools of modern medical science to examine the ancient descriptions of the symptoms suffered by King Jehoram who was affected by some disease. The Biblical texts were examined, and passages relating to the disease that afflicted King Jehoram, who ruled in Jerusalem 843-851 B.C., were closely studied. We have not included any commentaries, but referred only to the words of the Bible exactly as written. The Passages ''...the Lord smote him in his bowels with an incurable disease in the process of time, after the end of two years, his bowels fell out by reason of his sickness: so he died of sore diseases'' indicate that the King suffered from some kind of disease which affected his bowels. Among the various diseases which may be associated with prolapse of the bowel, colorectal carcinoma is the most acceptable. It seems that the colorectal carcinoma was poorly differentiated, invaded perirectal adipose tissue, blood vessels, and/or lymphatic vessels, and/or perineural areas, was lymph node positive and reached the 4th stage with the spread of metastases to the distal organs. Viewed by a modern physician, the story of King Jehoram unfolds as possibly the earliest description of a patient afflicted by colorectal carcinoma.

Epidemic anthrax in the eighteenth century, the Americas.

Anthrax has been described as a veterinary disease of minor importance to clinical medicine, causing occasional occupational infections in single cases or clusters. Its potential for rapid and widespread epidemic transmission under natural circumstances has not been widely appreciated. A little-known 1770 epidemic that killed 15,000 people in Saint-Domingue (modern Haiti) was probably intestinal anthrax. The epidemic spread rapidly throughout the colony in association with consumption of uncooked beef. Large-scale, highly fatal epidemics of anthrax may occur under unusual but natural circumstances. Historical information may not only provide important clues about epidemic development but may also raise awareness about bioterrorism potential.

Professions and intestinal infections in 15th-century Florence.

The aims behind this study are to verify a possible relationship between intestinal infectious diseases and certain professional activities carried out in 15th-century Florence by some categories of lesser labourers. Sources of the present study were the Libri dei Morti by the Florentine Ufficio della Grascia concerning the years 1424-25 and 1430 characterized by a plague epidemic. In this period, thanks to the particular social and economic circumstances of the times, the Libri dei Morti were enriched with additional notes about the illness that caused the deaths. The tables show an analysis of the data concerning the types of illness, the residence of the deceased and his/her social state. The present study suggests that certain professions were more exposed to infectious pathologies.

[A remembrance of Clarín's illnesses in his centenary]. / Las enfermedades de Clarín. Un recuerdo en su centenario.

The Spanish famous writer Leopoldo Alas, also known by the pseudonymous of "Clarín" suffered from two main kind of illnesses: nervous and digestives. Both began early, when he was only thirty two. At that moment, and during all his thirties, nervous ailments were conspicuous, but digestive problems were growing up slow but steadily and became the most serious and even menacing during his forties. Nervous pathology was double: on the one hand, some attacks of migraine with visual disturbances (scotoma), dysphasia and other "indescribable nervous oddities", which happened about 4-5 times per year; on the other, several emotional and vague symptoms, such as melancholia, dejected mood, anxiety, nervousness, etc. Digestive symptomatology, consisting of atonic constipation, intestinal dyspepsia, febricula, and a feeling of being "as a blocked drain", is due--no doubt--to tuberculous peritonitis diagnosed by his young nephew Dr. Martínez. This serious illness was the cause of his death on the 13th June 1901, when he was only 49.